GENETIC POLYMORPHISMS OF DRUG-METABOLIZING-ENZYMES AND LUNG-CANCER SUSCEPTIBILITY

A close association of smoking-associated lung cancer incidence with t he Msp I and Ile-Val polymorphisms of CYP1A1 gene was found in a Japan ese population in terms of genotype frequency comparison and cigarette dose response. A synergistic increase in susceptibility to lung cance r was observed when the susceptible genotypes of CYP1A1 were combined with a deficient GSTM1 genotype. Individual difference in expression l evels of Ahr and Arnt mRNAs was observed, and the expression levels of CYP1A1 appeared to associate with those of transcriptional factors, T he Ahr protein has two different structures, ascribed to one amino aci d replacement at codon 554 of Arg by Lys. However, this germ line poly morphism did not show a significant association with AHH inducibility nor lung cancer incidence, The p53 gene alterations in lung cancer tis sues were more frequently observed among the patients with a susceptib le allele of CYP1A1 gene.